Projects per year
Abstract
Platelets play a fundamental role in hemostasis and thrombosis. They are also involved in pathologic conditions resulting from blocked blood vessels, including myocardial infarction and ischemic stroke. Platelet adhesion, activation, and aggregation at sites of vascular injury are regulated by a diverse repertoire of tyrosine kinase–linked and G protein–coupled receptors. Src family kinases (SFKs) play a central role in initiating and propagating signaling from several platelet surface receptors; however, the underlying mechanism of how SFK activity is regulated in platelets remains unclear. CD148 is the only receptor-like protein tyrosine phosphatase identified in platelets to date. In the present study, we show that mutant mice lacking CD148 exhibited a bleeding tendency and defective arterial thrombosis. Basal SFK activity was found to be markedly reduced in CD148-deficient platelets, resulting in a global hyporesponsiveness to agonists that signal through SFKs, including collagen and fibrinogen. G protein–coupled receptor responses to thrombin and other agonists were also marginally reduced. These results highlight CD148 as a global regulator of platelet activation and a novel antithrombotic drug target
Original language | English |
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Pages (from-to) | 4942-4954 |
Number of pages | 13 |
Journal | Blood |
Volume | 113 |
Issue number | 20 |
DOIs | |
Publication status | Published - 14 May 2009 |
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Dive into the research topics of 'The tyrosine phosphatase CD148 is an essential positive regulator of platelet activation and thrombosis'. Together they form a unique fingerprint.Projects
- 4 Finished
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Investigating the Functional Roles of SH2 Domain-Containing Protein Tyrosine Phosphatases in Platelets
Senis, Y. & Watson, S.
1/01/09 → 31/12/12
Project: Research
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Regulation of platelet and endothelial cell surface receptors by tetraspanin microdomains
1/01/09 → 31/12/13
Project: Research
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Tetraspanin Superfamily Proteins in Megakaryocytes and Platelets
1/04/05 → 31/03/08
Project: Research Councils
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Adhesion receptors in the vasculature: from mouse to human
1/04/04 → 31/03/09
Project: Research Councils